Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI), scrapie, mink encephalopathy (TME), chronic wasting disease of deer and elk (CWD), bovine spongiform encephalopathy (BSE), and feline spongiform encephalopathy (FSE) all have been experimentally transmitted to nonhuman primates and laboratory rodents (mice and hamsters). We have classified them as the transmissible spongiform encephalopathies (TSEs). They are characterized by a long incubation period of from several months to more than 30 years, a degenerative pathology of the brain associated with the deposition of an insoluble form of a normal cell syaloglycoprotein known as prion protein (PrP). The definitive nature of the infectious agent if TSEs remains unknown. During this reporting period we have continued our studies to: identify the nature of the infectious agent; developing an improved diagnostic test for the TSEs; characterizing PrP and its gene and understanding the changes in the protein that are associated with infections, studying peripheral and CNS pathogenesis; determining natural modes of transmission; studying the genetic of resistance/susceptibility; and, methods of inactivating TSE agents.